This invention relates to the area of diagnosis, prognosis, and treatment of cancer, tumor progression, hyperproliferative cell growth, and accompanying physical and biological manifestations. More specifically, the invention includes polynucleotides that are differentially regulated in prostatic disorders, such as metastatic prostate cancer, localized prostate cancer, and benign prostate hyperplasia (BPH).
Genes that are up- or down-regulated in cancer or tumor progression are useful for therapeutic and diagnostic purposes. For example, detection of genes or gene expression products up-regulated in hyperproliferative cells can be a predictive or diagnostic marker of the onset or the progression of cancer. Early diagnosis can be useful if the cancer, tumors, or hyperproliferating cells can be inhibited, removed, or terminated to prevent metastasis or recurrence of cancerous growth. Such early warning is of particular use to prostate cancer patients, where removal of the growth, tumor, or cells is beneficial if the disease is confined to the prostate. There is a need in the art for genes related to cancer and tumor progression.
The present invention provides methods and reagents for diagnosing cancer, tumor progression, hyperproliferative cell growth, and accompanying biological and physical manifestations. Reagents for such diagnostic kits include:
(a) polynucleotides comprising a sequence capable of hybridizing to one or more of SEQ ID NO: 1-339 or complement thereof;
(b) polypeptides comprising the amino acid sequence encoded by any one of SEQ ID NO: 1-339; and
(c) antibodies capable of binding polypeptides comprising the amino acid sequence of (b).
The methods of diagnosis of the present invention include both nucleic acid assays and immunoassays.
In another embodiment, the present invention provides both compositions and methods for treating or ameliorating cancer, tumor progression, hyperproliferative cell growth, and accompanying biological and physical manifestations. The compositions for treatment or amelioration include:
(a) polynucleotides comprising the sequence capable of hybridizing to one or more of the sequences shown in SEQ ID NO:1-339 and complement thereof, including antisense, ribozyme and gene therapy nucleic acid constructs;
(b) polypeptides comprising the amino acid sequence encoded by any one of SEQ ID NO: 1-339; and
(c) antibodies capable of binding polypeptides of polypeptides comprising the amino acid sequence (b).
Methods of treatment or amelioration include administering compositions of polynucleotides, polypeptides, antibodies, or combinations thereof and can be used
(a) to inhibit translation and/or transcription;
(b) to inhibit biological activity;
(c) as a vaccine antigen; and
(d) as an immune system inducer.
Such compositions can be administered systemically or locally to the desired site.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of
(a) any one of SEQ ID NOs:2, 5, 49, 50, 99, 100, 115, 116, 118, 130, 131, 140, 144, 145, 146, 157, 158, 159, 163, 164, 165, 166, 177, 178, 180, 211, 212, 213, 218, 219, 220, 221, 229, 232, 233, 242, 243, 248, 249, 254, 256, 257, 259, 272, 273, 277, 288, 289, 292, 293, 316, 317, and 330;
(b) a polynucleotide that encodes a variant of the polypeptide encoded by (a); and
(c) a polynucleotide encoding a protein expressed by a polynucleotide having the sequence of any one of the sequences of (a).
Preferably, the nucleic acid obtained from the biological material of part (b) above is genomic DNA or mRNA. The nucleic acid can also be cDNA complementary to the mRNA.
Another embodiment of the invention is the use of the isolated polynucleotides or parts thereof as diagnostic probes or as primers.
In another embodiment, the present invention provides a composition comprising a polypeptide, wherein said polypeptide is selected from the group consisting of:
(a) a polypeptide encoded by any one of SEQ ID Nos:2, 5, 49, 50, 99, 100, 115, 116, 118, 130, 131, 140, 144, 145, 146, 157, 158, 159, 163, 164, 165, 166, 177, 178, 180, 211, 212, 213, 218, 219, 220, 221, 229, 232, 233, 242, 243, 248, 249, 254, 256, 257, 259, 272, 273, 277, 288, 289, 292, 293, 316, 317, and 330;
(b) a polypeptide encoded by full-length mRNA or cDNA corresponding to any one of SEQ ID NO: 1-339; and
(c) a variant of the protein (a) or (b);
In certain preferred embodiments, the polynucleotide is operably linked to an expression control sequence. The invention further provides a host cell, including bacterial, yeast, insect and mammalian cells, transformed with the polynucleotide sequence. The invention also provides the fill-length cDNA and the full length human gene corresponding to the polynucleotide.
Protein and polypeptide compositions of the invention may further comprise a pharmaceutically acceptable carrier. Compositions comprising an antibody that specifically reacts with such protein or polypeptide are also provided by the present invention.
The invention further relates to a polypeptide or nucleic acid obtained by transforming a host cell with nucleic acid comprising at least one of SEQ ID NO: 1-339, culturing the host cell, and recovering the replicated nucleic acid, the expressed RNA, and/or the expressed polypeptide.